Biofilm formed around dental implants trigger inflammation, which plays a leading role into promoting osteoclast mediated bone resorption and inhibiting bone formation, resulting in net bone loss around implants referred to as peri-implantitis. Once established, peri-implantitis progresses and leads to implant loss. The use of low temperature plasma (LTP) as a co-adjuvant to treat peri-implantitis is promising, as unlike current peri-implantitis treatment strategies and demonstrated by our preliminary data, has the unique potential to simultaneously (i) decontaminate infected surfaces while (ii) allowing for the creation of a suitable environment for bone regrowth around the implant (iii) without damaging peri-implant related tissues. Advantages of LTP over traditional antimicrobial applications are that LTP can be used for site-specific treatment, provides an almost instantaneous bactericidal response, antimicrobial resistance is less likely to occur, and there are minimal side effects. Our hypothesis is that LTP, coupled with surgical debridement, is a unique efficacious approach for treatment of peri-implantitis. To address our hypothesis, the following specific aims are proposed: Aim 1) To determine the LTP protocol most disruptive to in vitro multispecies peri-implantitis related biofilms, while maintaining low cytotoxicity. Biofilms in several levels of maturation comprising of Streptococcus oralis, Actinomyces naeslundii, Veillonela dispar, and Porphyromonas gingivalis will be treated with LTP in different conditions and compared to controls, which includes gas flow, 0.12% Chlorhexidine, 14 g/mL of amoxycillin and 140 g/mL metronidazole, individually or in combination. Efficacy, in the absence of toxicity, will be confirmed using in vitro reconstituted oral (ROE) and gingival epithelium (RGE) infected or not with P. gingivalis; Aim 2) To evaluate the effect of LTP treatment on peri-implantitis using a Gottingen minipig model. Ligature induced peri-implantitis will be developed in the jaws of miniature swine. These will be surgically treated coupled with two LTP regimens or with appropriate controls, allowed to heal, and the level of both soft and hard tissue reattachment evaluated by histology assays and three-dimensional image reconstruction. Anabolic and catabolic events will also be assessed. The proposed project will expand on our preliminary experiments and refine a unique approach for the treatment of emerging problem of peri-implantitis, using LTP?s synergistic effects to decontaminate and/or detoxify the infected peri- implantitis site, and create a suitable environment for bone regrowth around the implant, all of this in a single and short time application (minutes) and low-toxicity to the mucosa. Furthermore, our proposed experiments will test LTP in a large preclinical animal model that is remarkably similar to humans allowing direct translation of findings toward clinical practice.